Tacrolimus inhibits vasoconstriction by increasing Ca(2+) sparks in rat aorta.
10.1007/s11596-016-1534-6
- Author:
Yu-fang CHEN
1
;
Chen WANG
2
;
Rui ZHANG
3
;
Huan WANG
3
;
Rong MA
3
;
Si JIN
3
;
Ji-zhou XIANG
3
;
Qiang TANG
4
Author Information
1. Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. yf_chen0507@163.com.
2. Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. 448758559@qq.com.
3. Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
4. Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. tangqiang_tjmu@hust.edu.cn.
- Publication Type:Journal Article
- Keywords:
Ca2+ sparks;
large-conductance Ca2+-activated K+ channels;
tacrolimus;
vasoconstriction
- MeSH:
Animals;
Aorta;
cytology;
metabolism;
physiology;
Calcium Signaling;
Cells, Cultured;
Large-Conductance Calcium-Activated Potassium Channels;
metabolism;
Male;
Muscle, Smooth, Vascular;
drug effects;
metabolism;
physiology;
Myocytes, Smooth Muscle;
drug effects;
metabolism;
Norepinephrine;
pharmacology;
Rats;
Rats, Sprague-Dawley;
Ryanodine;
pharmacology;
Tacrolimus;
pharmacology;
Vasoconstriction
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2016;36(1):8-13
- CountryChina
- Language:English
-
Abstract:
The present study attempted to test a novel hypothesis that Ca(2+) sparks play an important role in arterial relaxation induced by tacrolimus. Recorded with confocal laser scanning microscopy, tacrolimus (10 µmol/L) increased the frequency of Ca(2+) sparks, which could be reversed by ryanodine (10 µmol/L). Electrophysiological experiments revealed that tacrolimus (10 µmol/L) increased the large-conductance Ca(2+)-activated K(+) currents (BKCa) in rat aortic vascular smooth muscle cells (AVSMCs), which could be blocked by ryanodine (10 µmol/L). Furthermore, tacrolimus (10 and 50 µmol/L) reduced the contractile force induced by norepinephrine (NE) or KCl in aortic vascular smooth muscle in a concentration-dependent manner, which could be also significantly attenuated by iberiotoxin (100 nmol/L) and ryanodine (10 µmol/L) respectively. In conclusion, tacrolimus could indirectly activate BKCa currents by increasing Ca(2+) sparks released from ryanodine receptors, which inhibited the NE- or KCl-induced contraction in rat aorta.
